How Brain Scans Might Change the Way Doctors Diagnose Alzheimer's

A new test can identify the disorder's early stages. How will it help patients?

man looking behind curtain

Davide Bonazzi

The way doctors diagnose Alzheimer's disease may be starting to change. Traditionally clinicians have relied on tests of memory and reasoning skills and reports of social withdrawal to identify patients with Alzheimer's. Such assessments can, in expert hands, be fairly conclusive—but they are not infallible. Around one in five people who are told they have the neurodegenerative disorder actually have other forms of dementia or, sometimes, another problem altogether, such as depression. To know for certain that someone has Alzheimer's, doctors must remove small pieces of the brain, examine the cells under a microscope and count the number of protein clumps called amyloid plaques. An unusually high number of plaques is a key indicator of Alzheimer's. Because such a procedure risks further impairing a patient's mental abilities, it is almost always performed posthumously.

In the past 10 years, however, scientists have developed sophisticated brain scans that can estimate the amount of plaque in the brain while people are still alive. In the laboratory, these scans have been very useful in studying the earliest stages of Alzheimer's, before overt symptoms appear. The results are reliable enough that last year the Food and Drug Administration approved one such test called Amyvid to help evaluate patients with memory deficits or other cognitive difficulties.

Despite the FDA's approval, lingering doubts about the exact role of amyloid in Alzheimer's and ambivalence about the practical value of information provided by the scan have fueled debate about when to order an Amyvid test. Not everyone who has an excessive amount of amyloid plaque develops Alzheimer's, and at the moment, there is generally no way to predict whom the unlucky ones will be. Recent studies have shown that roughly one third of older citizens in good mental health have moderate to high levels of plaque, with no noticeable ill effects. And raising the specter of the disorder in the absence of symptoms may upset more people than it helps because no effective treatments exist—at least not yet.

A new clinical trial will investigate whether giving an experimental drug as soon as the scans detect the formation of plaques can slow or halt the development of Alzheimer's. Even if the results are encouraging, a new drug will take many years to reach the market, and doctors must still determine how to use the scan responsibly in the meantime. “The whole field is grappling with this,” says neurologist Reisa Sperling of Brigham and Women's Hospital. She thinks the scan could bring clarity to challenging diagnoses, but “as a predictive test, it's not ready.”

Telltale Trouble
Scientists first linked amyloid plaques to what is now called Alzheimer's disease more than 100 years ago. In 1906 German psychiatrist Alois Alzheimer documented unusual protein knots in the brain of a deceased dementia patient. By the mid-1980s scientists determined that such plaques are made up of a protein they named beta-amyloid.

Healthy neurons produce plenty of beta-amyloid, but its precise purpose remains a mystery. In the initial stages of Alzheimer's and other neurodegenerative disorders, the proteins begin to behave strangely, sticking together to form larger and larger clumps. Scientists are still unsure whether the resulting plaques are primarily responsible for the devastating loss of millions of neurons that characterizes Alzheimer's or whether they are, instead, a by-product of some other, as yet undetermined, cause.

Nevertheless, the clumps form long before any explicit signs of dementia, and numerous plaques remain one of the best indicators of the disorder. Neurologists John C. Morris, Randall Bateman and their colleagues at Washington University in St. Louis have been tracking the health of people with a rare genetic mutation that guarantees Alzheimer's will strike them at a young age. They have detected amyloid plaques in the brain 15 years before cognitive problems typically appear in such individuals.

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This article was originally published with the title "Scanning for Alzheimer's."

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